SUMMARY / ABSTRACT The main goal of this project is to develop an ultrahigh field (UHF) magnetic resonance imaging (MRI) platform for molecular imaging as an increasingly sensitive molecular imaging platform to visualize, characterize, and measure biological processes at the molecular and cellular levels. We will realize the advantages of increases signal-to-noise ratio and spectral dispersion afforded by increased static magnetic fields while overcoming its multiple challenges through the development of novel system solutions, acquisition methods and reconstruction strategies. This platform will be developed on a unique 10.5T whole body MRI scanner and will make use of advanced radiofrequency (RF) management afforded by a 16 channel parallel transmit (pTx) system. Three specific molecular imaging strategies we will pursued in this project, each detailed in a specific aim. In SA1, we will develop a platform for integrated and advanced multinuclear applications at UHF where the proton (1H) channel can transmit more efficiently using pTx and the single x-nuclei channel (i.e. 31P, 23Na, or 13C) can either be used within the same session or the same scan, the later enabling advanced multinuclear applications. This functionality currently does not exist on current systems and is mandatory for 10.5T. In SA2, we will use pTx RF pulse design methods to create novel accelerated spatial-spectral pulses for improved spectroscopic imaging studies with reduced transmit field sensitivity, B0 sensitivity and echo times. Model-based reconstruction strategies will then allow us accelerate the acquisitions while providing improved estimates of metabolite and compartment specific, parameters such as T2 and/or diffusion which are correlated with both aging and disease. In SA3, we will use dynamic RF shimming and RF pulse design strategies to improve the magnetization preparation for rotating frame relaxation methods used to probe molecular dynamics. Readout and reconstruction strategies will also be explored to improve SNR efficiency and to accelerate relaxation rate mapping. Finally in both SA1 and SA3 we will explore the use and optimization of ultrashort echo time imaging methods to capture signals from short T2 spins as when imaging sodium or when trying to measure the relaxation rate properties of myelin. In total, the development of this molecular imaging platform will provide unparalleled functionality and sensitivity to probe molecular parameters to characterize tissue through molecular dynamics, spatial distributions of functional metabolic parameters and advanced multinuclear studies. The developed technologies will enhance the driving collaborative projects which focus on exploring new biomarkers to diagnose disease, monitor progression and evaluate treatment response in a variety of pathologies including osteoarthritis, multiple sclerosis, Alzheimer's and cancer. While the main focus is on the implementation of these methods at 10.5T for the highest sensitivity gains, the methods can positively impact 7T systems and in some cases even lower fields.